Coordinated activation of DNMT3a and TET2 in cancer stem cell-like cells initiates and sustains drug resistance in hepatocellular carcinoma.

BACKGROUND: Resistance to targeted therapies represents a significant hurdle to successfully treating hepatocellular carcinoma (HCC). While epigenetic abnormalities are critical determinants of HCC relapse and therapeutic resistance, the underlying mechanisms are poorly understood. We aimed to address whether and how dysregulated epigenetic regulators have regulatory and functional communications in establishing and maintaining drug resistance. METHODS: HCC-resistant cells were characterized by CCK-8, IncuCyte Live-Cell analysis, flow cytometry and wound-healing assays. Target expression was assessed by qPCR and Western blotting. Global and promoter DNA methylation was measured by dotblotting, methylated-DNA immunoprecipitation and enzymatic digestion. Protein interaction and promoter binding of DNMT3a-TET2 were investigated by co-immunoprecipitation, ChIP-qPCR. The regulatory and functional roles of DNMT3a and TET2 were studied by lentivirus infection and puromycin selection. The association of DNMT and TET expression with drug response and survival of HCC patients was assessed by public datasets, spearman correlation coefficients and online tools. RESULTS: We identified the coordination of DNMT3a and TET2 as an actionable mechanism of drug resistance in HCC. The faster growth and migration of resistant HCC cells were attributed to DNMT3a and TET2 upregulation followed by increased 5mC and 5hmC production. HCC patients with higher DNMT3a and TET2 had a shorter survival time with a less favorable response to sorafenib therapy than those with lower expression. Cancer stem cell-like cells (CSCs) displayed DNMT3a and TET2 overexpression, which were insensitive to sorafenib. Either genetic or pharmacological suppression of DNMT3a or/and TET2 impaired resistant cell growth and oncosphere formation, and restored sorafenib sensitivity. Mechanistically, DNMT3a did not establish a regulatory circuit with TET2, but formed a complex with TET2 and HDAC2. This complex bound the promoters of oncogenes (i.e., CDK1, CCNA2, RASEF), and upregulated them without involving promoter DNA methylation. In contrast, DNMT3a-TET2 crosstalk silences tumor suppressors (i.e., P15, SOCS2) through a corepressor complex with HDAC2 along with increased promoter DNA methylation. CONCLUSIONS: We demonstrate that DNMT3a and TET2 act coordinately to regulate HCC cell fate in DNA methylation-dependent and -independent manners, representing strong predictors for drug resistance and poor prognosis, and thus are promising therapeutic targets for refractory HCC.

Multiplexed electrochemical aptasensor based on mixed valence Ce(III, IV)-MOF for simultaneous determination of malathion and chlorpyrifos.

In this work, a multiplexed electrochemical aptasensor based on mixed valence Ce-MOF was constructed for the simultaneous determination of malathion and chlorpyrifos. Firstly, Ce(III, IV)-MOF materials with many catalytic sites were synthesized and characterized by SEM, TEM, XPS, FT-IR, XRD, and UV-Vis. Then, the chlorpyrifos and malathion signal markers based on Ce(III, IV)-MOF were prepared using thionine (Thi) and ferrocene (Fc) used as the electrochemical probe. The electrochemical signal was amplified by the reduction of thionine catalyzed by the spontaneous cycle of Ce(III, IV) in Ce(III, IV)-MOF skeleton and the reduction of ferrocene catalyzed by ascorbic acid (AA) in solution. The detection of the two targets did not interfere with each other, and the quantitative detection was realized with high sensitivity. The detection range of chlorpyrifos and malathion were 1.0 µM ∼ 0.1 pM, and the detection limits of chlorpyrifos and malathion were 0.038 and 0.045 pM (S/N = 3), respectively. The sensor provided a new idea for the simultaneous determination of multi-component and had a high application prospect in the field of food safety in the future.

Theoretical Study of Adsorption Behavior of Dimethylamine and Ammonia on Al- and Ga-Doped BN Monolayer Surfaces Based on DFT.

Endogenous volatile organic compounds (VOCs) can reflect human health status and be used for clinical diagnosis and health monitoring. Dimethylamine and ammonia are the signature VOC gases of nephropathy. In order to find a potential gas sensitivity material for the detection of both signature VOC gases of nephropathy, this paper investigated the adsorption properties of dimethylamine and ammonia on Al- and Ga-doped BN monolayers based on density functional theory. Through analyzing the adsorption energy, adsorption distance, charge transfer, density of states, and HOMO/LUMO, the results indicated that the adsorption effect of Al- and Ga-doped BN monolayers to dimethylamine and ammonia is probably good, and these nanomaterials have the potential to be applied for nephropathy monitoring and clinical diagnosis.

Flap endonuclease 1 (FEN1) as a novel diagnostic and prognostic biomarker for gastric cancer.

OBJECTIVE: Flap endonuclease 1 (FEN1) overexpression has been reported to be closely associated with cancer prognosis. However, its diagnostic and prognostic significance in gastric cancer (GC) has not yet been explored. METHODS: FEN1 expression, its correlation with clinical parameters, and prognostic significance were investigated by data mining of The Cancer Genome Atlas (TCGA) datasets. Patients were divided into low- and high-expression groups using the median value of FEN1 expression as the cut-off. The diagnostic value of FEN1 expression in GC tissues was determined via receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to identify the prognostic indicators. Gene set enrichment analysis (GSEA) was used to explore FEN1-related signalling pathways in GC. Furthermore, the Human Protein Atlas (HPA) database and GSE62254 dataset were used for further external validation. RESULTS: FEN1 was expressed at a higher level in GC tissues than in normal gastric tissues with high diagnostic accuracy (area under the ROC=0.909). Higher FEN1 expression was also validated at the protein level using the HPA database. High FEN1 expression in GC was correlated with older age (P<0.05). Patients with high FEN1 expression had a favourable prognosis compared to patients with low FEN1 expression (P=0.0048). Univariate and multivariate analyses revealed that FEN1 was an independent predictive factor associated with overall survival in both the TCGA cohort and the GSE62254 dataset (P=0.0004 and P=0.011, respectively). GSEA identified that the FEN1 expression was related to DNA replication, cell cycle, cytosolic and sensing pathways, oocyte meiosis, and the P53 signalling pathway. CONCLUSION: The results revealed high expression of FEN1 in GC; thus, it could be a promising early diagnostic and independent prognostic biomarker for GC.

The Challenge of Cross-Cultural Care Encounters: Perspective of Imported Nurses in Lhasa, Tibet.

AIMS: The purpose of this study was to describe the challenge of cross-cultural care encounters from perspective of imported nurses in Lhasa, Tibet, as well as investigate the relationship of cross-cultural care encounters and its influencing factors. METHODS: A cross-sectional survey was designed among 300 imported nurses and 255 patients selected from four comprehensive hospitals (including two Grade III Class A hospitals and two Grade III Class B hospitals) in Lhasa. The average number, standard deviations, constituent ratios, T-tests, rank-sum tests, one-way ANOVAs, multiple stepwise regression analyses, and Pearson correlation analysis were used to analyze cross-cultural care encounters and its influencing factors. P < 0.05 was considered statistically significant. RESULTS: The cross-cultural care encounter of nurses was 61.73 ± 11.86, mainly relating to age, technical titles, Tibetan language ability, and participation in humanistic training. Age, gender, educational level, technical titles, Tibetan language ability, years working in Tibet, and participation in language and humanities training were the influencing factors (P < 0.05). The average total score of culturally competent care of imported nurses in Lhasa was 218 ± 31.09. Cross-cultural care encounters of nurses were positively correlated with culturally competent care (r = 0.126, P < 0.01) and the needs of patients' cultural care (r = 0.183). CONCLUSION: The scores of culturally competent care and cross-cultural care encounter of imported nurses were at a high level, and their culturally competent care was in the second stage of "conscious and incapable" status. The cross-cultural care encounter of nurses is positively related to culturally competent care and the needs of patients' cultural care. Abilities of language communication, understanding of Tibetan culture, and enhancement of the cultural ability needed optimization.

A label-free electrochemical aptasensor based on 3D porous CS/rGO/GCE for acetamiprid residue detection.

A novel label-free electrochemical aptasensor was fabricated based on a three-dimensional porous electrode (3D-CS/rGO/GCE) for the detection of acetamiprid residues. The sensing signal was generated by the DNA itself. The porous electrode was prepared by electrodeposition in situ and characterized by scanning electron microscope (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). These results indicated that the porous electrode has a uniform nanoporous structure, high active area, and excellent conductivity, leading to improve the transmission efficiency of current signals. The 3D-CS/rGO/GCE was used to increase a load of acetamiprid aptamer on the electrode. Meanwhile, DNA self-assembly strategy was used to further increase the DNA amounts. Thus the electrochemical current was amplified significantly due to increased phosphate group amounts by the above synergistic effect. The determination of acetamiprid residues using square wave voltammetry (SWV) showed good sensitivity, with the linear range from 0.1 pM to 0.1 µM and the detection limit was 71.2 fM. The label-free electrochemical aptasensor was also used to detect acetamiprid residues in tea samples with satisfactory results.

Prognostic nomogram based on log odds of positive lymph nodes for gastric carcinoma patients after surgical resection.

Aim: To build a prognostic nomogram based on log odds of positive lymph nodes for patients with gastric carcinoma (GC) after resection, and to compare the predictive performance with the American Joint Committee on Cancer (AJCC) staging system and lymph node ratio (LNR). Methods: Multivariate analyses were performed to identify the independent variables for cancer-specific survival (CSS). A nomogram was constructed based on independent clinicopathological factors. Results: The C-indices for predicting CSS were 0.674 in development cohort and 0.647 in validation cohort, which were higher than that of the AJCC staging system and LNR. Conclusion: The nomogram was more accurate than the AJCC staging system and LNR for predicting CSS in patients undergoing resection for GC.

The effect of mobile applications for improving adherence in cardiac rehabilitation: a systematic review and meta-analysis.

BACKGROUND: Despite of the established effectiveness, the acceptance and adherence of cardiac rehabilitation (CR) remains sub-optimal. Mobile technologies are increasingly used in promoting CR without any firm evidence of their safety and efficacy. This systematic review and meta-analysis were aimed to assess the effect of mobile applications as an intervention for improving adherence to CR. METHODS: Relevant studies were searched in PubMed, the Cochrane Library, Embase and Web of Science from inception to 29th December 2018. Eligible studies were the ones which used mobile applications as a stand-alone intervention or as the primary component for the intervention directed at improving CR adherence, without any limitations on outpatient or home-based CR. RESULTS: Eight studies were eligible for the systematic review including four randomized controlled trials (RCTs) as well as four before-after studies of which only one had control group. Four RCTs and 185 patients in experimental group were included in meta-analysis, which had evaluated the effect of mobile health applications on CR completion and had reported that the adherence of patients using mobile applications was 1.4 times higher than the control group (RR = 1.38; CI 1.16 to 1.65; P = 0.0003). Moreover, we also found mixed results in exercise capacity, mental health and quality of life. CONCLUSION: The use of mobile applications for improving the adherence of the CR might be effective. However, it appears to be in the initial stage of implementing mobile applications in CR and more research is essential to validate their effectiveness.

Hyposmia as a Predictive Marker of Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Hyposmia is one of the most common and best-characterized conditions that is also one of the first nonmotor features of Parkinson's disease (PD). The association of hyposmia with PD is widely accepted; however the likelihood of developing PD is unclear. Our meta-analysis aimed to investigate the risk of PD in individuals with hyposmia. METHODS: Prospective studies on humans published before December 4th, 2018, were searched for in PubMed, Embase, Web of Science, and Cochrane Library databases. Two independent reviewers screened studies for inclusion and extracted data. We assessed the quality of studies using the Newcastle-Ottawa Scale and pooled data for analysis using random-effects models. RESULTS: Of the 1774 studies retrieved, seven met the inclusion criteria for this review. A total of 3272 hyposmia and 176 PD events were reported over follow-up periods ranging from 3 to 17 years. Hyposmia was associated with a 3.84-fold risk of developing PD (pooled relative risk: 3.84, 95% CI 2.12-6.95). Subgroup analyses identified few differences between different hyposmia assessment methodologies and follow-up periods. CONCLUSIONS: Our findings suggest that deficiencies in olfaction are associated with an increased risk of developing PD. Future studies are needed to investigate whether hyposmia is a promising and feasible biomarker for the early diagnosis of PD.

Dual-Signaling Amplification Electrochemical Aptasensor Based on Hollow Polymeric Nanospheres for Acetamiprid Detection.

In this work, we first reported a dual-signaling electrochemical aptasensor based on layer-by-layer template technology and catalytic amplification for acetamiprid detection. Herein, the signal probe of the ferrocene (Fc)-based hollow polymeric nanospheres (Fc-HPNs) were prepared with repeated electrostatic adsorption between anionic poly(acrylic acid) and hyperbranched cationic polyethylenimine. In addition, ascorbic acid (AA) as an enhancer can catalyze the reduction of Fc-HPNs, which results in significant enhancement of the oxidation peak current of Fc-HPNs. Remarkably, the Fc-HPNs played dual roles: as nanocarriers to significantly increase the load amount of Fc and as nanoreducers to effectively catalyze reduction by AA for further signal amplification. Therefore, because of the special nanostructures of Fc-HPNs and the effective catalytic effect of AA, a dual-signaling electrochemical aptasensor was proposed. Surprisingly, this proposed assay for trace amounts of target detection exhibits excellent sensitivity with a linear range from 10 nM to 1 fM and a limit of detection down to 0.33 fM (S/N = 3), which opened a novel avenue and versatile strategy for monitoring of acetamiprid.

A dual amplification electrochemical immunosensor based on HRP-Au@Ag NPs for carcinoembryonic antigen detection.

A sensitive sandwich-type electrochemical immunosensor based on dual amplification strategy was constructed. The dual amplification strategy has been used secondary antibody(Ab2)-horseradish peroxidase(HRP)-Au@Ag nanoparticles (Au@Ag NPs) for carcinoembryonic antigen(CEA) detection. Ab2-HRP-Au@Ag NPs as dual amplification markers triggered the disproportionation of H2O2, which could facilitate the catalytic oxidation of hydroquinone to quinone(BQ). In addition, due to their large surface area and excellent conductivity, nitrogen-doped graphene were used as a platform to firmly assemble primary antibody (Ab1). Above mentioned generated amout of BQ are corresponding to trace CEA, resulting in the highly electrochemical reduction signal. Under the optimal conditions, the linear range of CEA concentration was 0.0001-100 ng mL-1, and the limit of detection (LOD) could be as low as 0.05 pg mL-1. Importantly, the immunosensor also showed acceptable stability, reproducibility and selectivity.

Exercise therapy in patients with constipation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Exercise therapy has shown significant efficacy as a means of treating various intestinal diseases, but its role in the treatment of constipation is still unclear. The purpose of this study was thus to analyze the effects of exercise on constipation by means of a systematic review and meta-analysis. METHODS: PubMed, Web of Science, EMBASE, Cochrane Library and three Chinese databases [Wanfang Database, Chinese Biomedical Literature (CBM) and China National Knowledge Infrastructure (CNKI)] were searched for relevant studies published through June 2018. Eligible studies were selected in accordance with the PRISMA statement. The main results of interest were changes in gastrointestinal symptoms. RESULTS: A total of nine randomized controlled trials involving 680 participants were included. Eight studies involved aerobic exercise and only one study involved anaerobic exercise. The aerobic exercises included were Qigong, walking and physical movement. The results of this systematic review and meta-analysis indicated that exercise had significant benefits as a means of improving the symptoms of constipation patients [relative risk (RR) = 1.97; 95% CI: 1.19, 3.27; p = .009; I2=91.3%]. Subgroup analyses showed that aerobic exercise (RR = 2.42; 95% CI: 1.34, 4.36; p = .000; I2=88%) similarly had a positive effect on constipation. However, these results were associated with a high risk of bias. CONCLUSION: Our results suggest that exercise may be a feasible and effective treatment option for patients with constipation. However, due to methodological shortcomings, the real effect of this intervention cannot be definitively determined. Researchers should, therefore, design more rigorous studies in order to evaluate the effect of exercise on constipation.

Ultrasensitive "signal-on" electrochemical aptasensor for assay of acetamiprid residues based on copper-centered metal-organic frameworks.

In present work, a versatile "signal-on" electrochemical aptasensor with ultra-sensitivity and high selectivity for detecting acetamiprid residues has been successfully constructed. Electrochemistry behaviors of as-synthesized copper-centered metal-organic frameworks (CuMOF) on various electrodes were investigated in details. The results indicated that CuMOF exhibited well-behaved redox events. Thus, we used Au-CuMOF as signaling element to label probe DNA (pDNA). The gold nanoparticles-reduced graphene oxide (Au-rGO) has a high specific surface area and excellent conductivity, which was utilized to immobilize complementary strand (cDNA). In the presence of acetamiprid, Au-CuMOF-labeled pDNA would hybridize with the exposed cDNA, allowing CuMOF to approach the electrode and produce a sensitive signaling current. Such a "signal-on" method does not suffer from the drawbacks of "signal-off" methods. The linear range of this proposed electrochemical aptasensor was 0.1 pM-10.0 nM and the detection limit was as low as 2.9 fM. This platform exhibited wonderful selectivity, stability, and repeatability, and was successfully applied to detect acetamiprid residues in tea samples exhibiting enormous practical application potential.

Validation of an information-motivation-behavioral skills model of upper limb functional exercise adherence among Chinese postoperative patients with breast cancer.

BACKGROUND: The adherence to postoperative upper limb functional exercise in breast cancer (BC) patients is poor which can lead to adverse health outcomes. Effective intervention content to improve adherence is still unclear. The information-motivation-behavioral skills (IMB) model is a theoretical model that has been widely used to promote health behavior in many disease populations and may, therefore, help to explain and promote adherence to functional exercise. In this study, we validated the IMB model in a sample of postoperative BC patients. METHODS: A cross-sectional study of 165 postoperative patients with BC was performed in a hospital. We collected information on demographics, functional exercise knowledge (information), personal and social motivation (motivation), objective skills and self-efficacy (behavioral skills), and functional exercise adherence (behavior). Measured variable path analyses were applied for the IMB framework. RESULTS: The IMB elements explained 37.9% of the variance in adherence. As predicted, behavioral skills had a direct effect on adherence (ß = 0.509; P < 0.05) and mediated the effects of knowledge (indirect effect 0.092, P < 0.05) and motivation (indirect effect 0.251, P < 0.05) on adherence. CONCLUSIONS: Behavioral skills have a direct effect on functional exercise adherence and a mediating effect on the influence of knowledge and motivation on adherence. Thus, these factors represent key determinants of exercise adherence. The IMB model could be applied to the upper limb exercise adherence of postoperative BC patients. These findings indicate that the promotion of exercise adherence interventions may benefit from targeting patients' exercise adherence-related knowledge, motivation, and behavioral skills.

Exercise therapy of patients with irritable bowel syndrome: A systematic review of randomized controlled trials.

BACKGROUND: As drug use has limitations in the treatment of irritable bowel syndrome (IBS), increasing attention is being paid to nondrug therapies and complementary treatments, especially exercise. It is known that bowel movements are more frequent and colon transit is more rapid in physically active individuals than in sedentary individuals. However, the effects of exercise on IBS are unclear. PURPOSE: We conducted a systematic review to assess the effects of exercise on IBS. METHODS: We searched PubMed, Web of Science, EMBASE, Cochrane Library, and two Chinese databases (Wanfang Database and Chinese Biomedical Literature [CBM]) for eligible studies. We extracted and pooled relevant information regarding the effects of exercise in patients with IBS. The primary outcomes were gastrointestinal symptoms, quality of life, depression, and anxiety. KEY RESULTS: A total of 683 patients with IBS from 14 randomized controlled trials met our inclusion criteria. The exercise interventions in this review were yoga, walking/aerobic physical activity, Tai Ji, mountaineering, and Baduanjin qigong activity. The results of this review suggested exercise had significant benefits for patients with IBS, but studies were limited by the strong risk of bias. CONCLUSIONS AND INFERENCES: Our findings suggest that exercise is potentially a feasible and effective treatment for IBS patients. However, because of methodologic issues, no firm conclusions could be drawn about the true effects of this intervention. Researchers should design a rigorous study to assess the effects of exercise on IBS.

UBA2 promotes proliferation of colorectal cancer.

Small ubiquitin­like modifier proteins are involved in tumorigenesis; however, the potential effects and functions of the family member ubiquitin­like modifier­activating enzyme 2 (UBA2) on colorectal cancer are not clear. The present study aimed to examine the effects of UBA2 on the proliferation of colorectal cancer cells in vitro and in vivo. The mRNA and protein expression levels of UBA2 in patients with colorectal cancer were measured by reverse transcription­quantitative polymerase chain reaction and immunohistochemistry, respectively. UBA2 expression levels in colorectal cancer tissues were significantly increased compared with the paracancerous normal tissues. The expression of UBA2 was also associated with higher stage colorectal cancer and poor prognosis. MTT and colony formation assays were used to examine proliferation in colorectal cancer cell lines. Flow cytometry was performed to examine the effects of UBA2 on the cell cycle and apoptosis of colorectal cancer cell lines and protein expression levels were examined by western blotting. Athymic nude mice were used to examine the ability of transfected colorectal cancer cells to form tumors in vivo. Downregulation of UBA2 inhibited the proliferation of colorectal cancer cell lines in vitro and in vivo through the regulation of cell cycle associated protein expression and apoptosis. Furthermore, downregulation of UBA2 decreased the expression levels of cyclin B1, B­cell lymphoma-2, phosphorylated protein kinase B and E3 ubiquitin­protein ligase MDM2 in colorectal cancer cells, whereas the expression levels of p21 and p27 were increased. UBA2 was demonstrated to serve an essential role in the proliferation of colorectal cancer and may be used as a potential biomarker to predict prognosis and as a therapeutic target in colorectal cancer.

Prognostic Value of Frailty for Older Patients with Heart Failure: A Systematic Review and Meta-Analysis of Prospective Studies.

OBJECTIVE: Numerous studies have investigated the prognostic role of frailty in elderly patients with heart failure (HF), but the limited size of the reported studies has resulted in continued uncertainty regarding its prognostic impact. The aim of this study was to integrate the findings of all available studies and estimate the impact of frailty on the prognosis of HF by performing a systematic review and meta-analysis. METHODS: PubMed, Embase, Cochrane, and Web of Science databases were searched from inception to November 8th 2017 to identify eligible prospective studies. The Newcastle-Ottawa Scale (NOS) was used to evaluate study quality. The association between frailty and HF outcomes was reviewed. Overall hazard ratios (HRs) for the effects of frailty on all-cause mortality were pooled using a fixed-effect model and publication bias was evaluated using funnel plots. RESULTS: A total of 10 studies involving 3033 elderly patients with HF were included in the systematic review and meta-analysis. All eligible studies indicated that frailty was of prognostic significance for HF patients. The HRs for the effects of frailty on all-cause mortality were 1.70 (95% confidence interval (CI): 1.41-2.04), based on the pooling of six studies that provided related data. However, publication bias was observed among the studies. CONCLUSIONS: Frailty has a high prevalence among older patients with HF. Elderly HF patients with frailty have a poorer prognosis than those without frailty. Further studies are now required to implement the use of frailty assessment tools and explore effective interventions for frailty in older HF patients.

Physical activity can improve cognition in patients with Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) is mainly characterized by decline of cognitive functions such as memory and learning, which has a high prevalence and poor drug efficacy in treatment regimes. A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to evaluate the effectiveness of exercise on cognitive function in patients diagnosed with AD. METHODS: The bibliographic databases (PubMed, Cochrane Library and Embase, and Web of Science) and four Chinese databases (Wanfang data, CBM, CNKI, and VIP) were searched to identify RCTs published in any language between January 1, 1960, and January 1, 2018. Only peer-reviewed articles and RCTs were included. The collected data were analyzed by Review Manager (5.3). RESULTS: Overall, 869 patients diagnosed with AD were included from 13 RCTs. Patients in the intervention group received pure exercise interventions and a cognitive test. Although there was heterogeneity in intervention methods and cognitive measures among studies, meta-analysis (seven studies) supports positive effects of physical activity on cognitive function of patients with AD (mean difference [MD] =2.53, the 95% CI=0.84 to 4.22, test for overall effect: Z=2.93 [P=0.003]). Eight studies demonstrated that exercise improves cognitive function for individuals with AD. However, the remaining five studies did not display a beneficial effect of exercise on cognitive function in patients with AD. CONCLUSION: This meta-analysis and systematic review indicated that exercise intervention might improve the cognitive function of AD or slow down the decline of cognition; however, this relationship was not always true across studies. RCTs with clear intervention criteria, large samples, and long-term follow-up are needed in the future to demonstrate the benefits of exercise for cognitive function in AD patients.

In Vivo Study of the Effects of ERß on Apoptosis and Proliferation of Hormone-Independent Prostate Cancer Cell Lines PC-3M.

OBJECTIVE: To evaluate the in vivo therapeutic effects of attenuated Salmonella carrying PCDNA3.1-ERß plasmid in hormone-independent prostatic cancer in nude mice and to clarify the mechanism by which estrogen receptor ß (ERß) induces apoptosis and proliferation in prostatic cancer cells in mice. METHODS: The orthotopic prostatic cancer models of mice were randomly divided as follows: MOCK group, treated with PBS, PQ group, treated with attenuated Salmonella alone, PQ-PCDNA3.1 group, treated with attenuated Salmonella carrying PCDNA3.1 plasmid, and PQ-PCDNA3.1-ERß group, treated with the attenuated Salmonella carrying PCDNA3.1-ERß plasmid. Then, 10 µl of the plasmid-containing solution, comprising 1 × 107 cfu of the bacteria, was administered via intranasal delivery to each group except the MOCK group. The experimental methods included flow cytometry and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay, immunohistochemistry, and western blotting. RESULTS: Compared with the MOCK, PQ, and PQ-PCDNA3.1 groups, the weights of tumors in the PQ-PCDNA3.1-ERß group were significantly reduced. The results of flow cytometry and TUNEL assay revealed that the number of apoptotic cells in the PQ-PCDNA3.1-ERß group significantly increased. Compared with PQ-PCDNA3.1 group, the protein expression levels of ERß, Bad, p-caspase 9, p-caspase 3, and cleaved PARP in the PQ-PCDNA3.1-ERß group were significantly increased, while the expression levels of Akt, p-Akt, and Bcl-xl were decreased (P < 0.05). CONCLUSION: The attenuated Salmonella carrying PCDNA3.1-ERß plasmid could inhibit the growth of orthotopic prostatic cancer in mice by increasing the expression of ERß.

Synchronous diffuse large B-cell lymphoma of the stomach and small cell lung carcinoma: A case report.

RATIONALE: The synchronous occurrence of lung cancer in patients with gastric neoplasms is relatively uncommon, especially the cases of synchronous coexistence of small cell lung carcinoma and diffuse large B-cell lymphoma of the stomach. PATIENT CONCERNS: We encountered a case of synchronous primary small cell lung carcinoma and diffuse large B-cell lymphoma of the stomach. A 63-year-old patient with a 7.5 × 5.09 cm mass in the superior lobe of the right lung diagnosed with small cell lung cancer and synchronous diffuse large B-cell lymphoma of the stomach. DIAGNOSES: The diseases were diagnosed by the pathological biopsy and immunohistochemical methods. INTERVENTIONS: As the patient received CHOP chemotherapy, pulmonary function deterioraed. Etoposide was added to the chemotherapy. OUTCOMES: However, after the first treatment, chest computed tomography showed that the mass in the superior lobe of the right lung had increased to 8.5 × 5.2 cm. LESSONS: This report draws attention to the fact that the treatment of synchronous tumors is a challenge.